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Updated: Jun 14, 2025
A Human Ex Vivo Atherosclerotic Plaque Model to Study Lesion Biology
Published on: May 6, 2014
A cross-sectional study comparing the expression of DNA repair molecules in subjects with and without atherosclerotic
Berk Arapi1, Selin Unal2, Narmina Malikova2
1Department of Cardiovascular Surgery Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey.
Background:
Atherosclerosis, serving as the primary pathological mechanism at the core of cardiovascular disease, is now widely acknowledged to be associated with DNA damage and repair, contributing to atherosclerotic plaque formation. Therefore, molecules involved in the DNA repair process may play an important role in the progression of atherosclerosis. Our research endeavors to explore the contributions of specific and interrelated molecules involved in DNA repair (APE1, BRCA1, ERCC2, miR-221-3p, miR-145-5p, and miR-155-5p) to the development of atherosclerotic plaque and their interactions with each other.
Methods & Results:
Gene expression study was conducted using the real-time polymerase chain reaction (qRT-PCR) method on samples from carotid artery atherosclerotic plaques and nonatherosclerotic internal mammary arteries obtained from 50 patients diagnosed with coronary artery disease and carotid artery disease. Additionally, 50 healthy controls were included for the determination of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Although no difference was observed in mRNA gene expressions, we noted a decrease in miR-155-5p gene expression (p = 0.003) and an increase in miR-221-3p gene expression (p = 0.015) in plaque samples, while miR-145-5p gene expression remained unchanged (p = 0.57). Regarding serum 8-OHdG levels, patients exhibited significantly higher levels (1111.82 ± 28.64) compared to controls (636.23 ± 24.23) (p < 0.0001).
Conclusions:
In our study demonstrating the role of miR-155-5p and miR-221-3p in atherosclerosis, we propose that these molecules are potential biomarkers and therapeutic targets for coronary artery diseases and carotid artery disease.
Insights
DNA repair molecules, specifically miR-155-5p and miR-221-3p, show altered expression in atherosclerosis. These microRNAs are potential biomarkers and therapeutic targets for cardiovascular and carotid artery diseases.
Area of Science:
- Biochemistry
- Molecular Biology
- Cardiovascular Research
Background:
- Atherosclerosis, a key factor in cardiovascular disease, is linked to DNA damage and repair processes.
- Molecules involved in DNA repair may influence the development of atherosclerotic plaques.
- This study investigates specific DNA repair molecules (APE1, BRCA1, ERCC2, miR-221-3p, miR-145-5p, miR-155-5p) and their roles in atherosclerosis.
Purpose of the Study:
- To explore the contribution of selected DNA repair molecules to atherosclerotic plaque development.
- To investigate the interactions between these DNA repair molecules in the context of atherosclerosis.
- To identify potential biomarkers and therapeutic targets for cardiovascular and carotid artery diseases.
Main Methods:
- Gene expression analysis using real-time quantitative polymerase chain reaction (qRT-PCR) on carotid artery plaque and internal mammary artery samples from 50 patients.
- Comparison with 50 healthy controls for serum 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels.
- Analysis of mRNA and microRNA (miRNA) expression, including miR-155-5p, miR-221-3p, and miR-145-5p.
Main Results:
- No significant difference in mRNA gene expressions was observed between plaque and non-plaque samples.
- A significant decrease in miR-155-5p expression (p=0.003) and a significant increase in miR-221-3p expression (p=0.015) were found in plaque samples.
- Serum 8-OHdG levels were significantly higher in patients (1111.82±28.64) compared to controls (636.23±24.23) (p<0.0001).
Conclusions:
- miR-155-5p and miR-221-3p play a role in the pathogenesis of atherosclerosis.
- These microRNAs represent potential biomarkers for diagnosing and monitoring atherosclerosis.
- Targeting miR-155-5p and miR-221-3p may offer novel therapeutic strategies for cardiovascular and carotid artery diseases.
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